Photodynamic therapy (PDT) and fluorescence imaging are non-invasive modalities for disease treatment and diagnosis, respectively. Both modalities require the use of a dye (light harvesting material) and light or source of excitation. A sensitizer is used in the case of PDT, while a fluorophore is used in the case of fluorescence imaging. The search for novel non-invasive regimen/agents using tissue penetrable light (e.g., at 600 nm-900 nm) to improve disease prognosis and therapy is expanding due to its advantages of reduced toxicity by avoiding non-ionized species, relatively low cost, and real time monitoring. In general, near infra-red (NIR) fluorescent probes and photosensitizers (PSs) for photodynamic diagnosis and therapy (PDD/PDT), respectively, are more effective than visible ones in the clinic due to deeper tissue penetration resulting from reduced absorption by cells/tissues and water, light scattering, and autofluorescence.
BODIPY (boron dipyrromethene difluoride, or 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) is a PS noted for high photostability, unique optical properties evidenced in sharp absorption and emission bands, high extinction coefficient, and high fluorescence quantum yields, as well as flexible synthesis and tunability. However, currently, among the BODIPY dyes used for PDT and in vivo imaging, none absorbs beyond 700 nm. Further, the synthesis of BODIPY derivatives has been complicated. It is to the development and use of NIR BODIPY dyes, and their production with greater ease and efficiency that the presently disclosed inventive concepts are presented.
In PDT a PS is administered and then the treatment site (e.g. tumor) is subjected to light irradiation to generate reactive oxygen species, especially singlet oxygen from oxygen, to damage target cells and tissues. When a PS is irradiated, it is converted to the triplet state via intersystem crossing from the singlet state. In what is known as the type II process, the triplet state PS transfers its energy to molecular oxygen to produce singlet oxygen. In a type I process, a chemical reaction of the excited PS with a substrate occurs, initiating an electron or proton transfer leading to the formation of radicals which react with molecular oxygen to produce reactive oxygen species such as superoxide, hydrogen peroxide, and hydroxyl ion.